TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling

Abstract

BackgroundTFAP2B is a member of the AP2 transcription factor family, which orchestrates a variety of cell processes. However, the roles of TFAP2B in regulating carcinogenesis remain largely unknown. Here, we investigated the regulatory effects of TFAP2B on lung adenocarcinomas growth and identified the underlying mechanisms of actions in non-small cell lung cancer (NSCLC) cells.MethodsWe first examined the expression of TFAP2B in lung cancer cell lines and tumor tissues. We also analyzed the prognostic predicting value of TFAP2B in lung adenocarcinomas. Then we investigated the molecular mechanisms by which TFAP2B knockdown or overexpression regulated lung cancer cell growth, angiogenesis and apoptosis, and further confirmed the role of TFAP2B in tumor growth in a lung cancer xenograft mouse model.ResultsTFAP2B was highly expressed in NSCLC cell lines and tumor tissues. Strong TFAP2B expression showed a positive correlation with the poor prognoses of patients with lung adenocarcinomas (P < 0.001). TFAP2B knockdown by siRNA significantly inhibited cell growth and induced apoptosis in NSCLC cells in vitro and in a lung cancer subcutaneous xenograft model, whereas TFAP2B overexpression promoted cell growth. The observed regulation of cell growth was accompanied by the TFAP2B-mediated modulation of the ERK/p38, caspase/cytochrome-c and VEGF/PEDF-dependent signaling pathways in NSCLC cells.ConclusionsThese results indicate that TFAP2B plays a critical role in regulating lung adenocarcinomas growth and could serve as a promising therapeutic target for lung cancer treatment.

TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management

“…This is particularly noteworthy, as recent studies have shown that TFAP2B has a significant role in the development of non-small cell lung cancer through mechanisms that involve VEGF-dependent signaling. 29 Defining when a genomic gain constitutes amplification of a particular gene of interest is a complex issue. There is no universal definition and thus defining amplification is often done on a tumor-bytumor basis.…”

Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling

“…VEGF initiates signaling pathways in ECs to promote proliferation, migration, survival and vascular permeability. VEGF inhibitors have been developed, as the overexpression of VEGF is frequently associated with a poorer prognosis in various types of cancer (28,29). Subsequent ELISA and western blot analyses also confirmed the cytokine changes reported in the human angiogenesis array.…”

Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma

“…TFAP2 proteins are RA‐inducible transcriptional activators (Luscher et al., 1989), and have been shown to play important roles during vertebrate development, cell growth and differentiation (Auman et al., 2002; Moser et al., 1997; Zeng et al., 1997; Zhang et al., 1996). In addition, alterations in TFAP2 expression patterns and both oncogenic and tumor suppressive functions have been described in various cancer entities (Fu et al., 2014; Pellikainen and Kosma, 2007). In neuroblastoma, expression of the TFAP2 gene family member TFAP2B , also known as AP‐2β, has been shown to be associated with low risk disease in small tumor cohorts (Fischer et al., 2006; Thorell et al., 2009).…”